Genetic Variant SBF2:c.1395+8_1395+11delAGTA (chr11-9989485-ATACT-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_030962.4(SBF2):c.1395+8_1395+11delAGTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,454,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SBF2
NM_030962.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.64

Publications

0 publications found

Variant links:

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4B2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

SBF2 links:

ENSG00000286561 (HGNC:):

ENSG00000286561 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-9989485-ATACT-A is Benign according to our data. Variant chr11-9989485-ATACT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 543477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SBF2	NM_030962.4	MANE Select	c.1395+8_1395+11delAGTA	splice_region intron	N/A	NP_112224.1
SBF2	NM_001386339.1		c.1395+8_1395+11delAGTA	splice_region intron	N/A	NP_001373268.1
SBF2	NM_001424318.1		c.1431+8_1431+11delAGTA	splice_region intron	N/A	NP_001411247.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SBF2	ENST00000256190.13	TSL:1 MANE Select	c.1395+8_1395+11delAGTA	splice_region intron	N/A	ENSP00000256190.8
SBF2	ENST00000533770.6	TSL:1	c.1395+8_1395+11delAGTA	splice_region intron	N/A	ENSP00000509247.1
SBF2	ENST00000526353.2	TSL:1	n.1545+8_1545+11delAGTA	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

246984

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000446

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000161

AC:

AN:

1302646

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

656528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30310

American (AMR)

AF:

0.00

AC:

AN:

43946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25038

East Asian (EAS)

AF:

0.00

AC:

AN:

38842

South Asian (SAS)

AF:

0.00

AC:

AN:

80992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5284

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

970370

Other (OTH)

AF:

0.0000546

AC:

AN:

54970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Charcot-Marie-Tooth disease type 4

Benign:1

Mar 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over